Background: Advanced-stage classical Hodgkin's lymphoma (cHL) is a curable malignancy, however up to 25% of patients may relapse following frontline multiagent-chemotherapy. Novel treatment options such as PD-1 inhibitors and antibody-drug conjugates (ADC) have demonstrated high efficacy with favorable safety profiles in frontline and relapsed cHL. Early reduction in volumetric and metabolic PET parameters have been reported as effective predictors of outcome in cHL. Here, we describe the changes in metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) after two cycles of therapies containing nivolumab, brentuximab vedotin (Bv), or both in advanced cHL.
Methods: We retrospectively enrolled subjects with newly diagnosed, advanced stage cHL who received therapy in three protocols: Bv-nivolumab-AD, Bv-AVD, or nivolumab-AVD. All protocols did not allow for radiation consolidation. Baseline (PET0) and interim PET after two cycles (PET2) were analyzed and cHL lesions were segmented using a threshold of 41% of the SUVmax. MTV, TLG, and SUVmax were recorded at both time-points and percentage changes were calculated as ΔMTV, ΔTLG, and ΔSUVmax, respectively. Summary statistics were reported, and Kurskal-Wallis test was used to compare PET-parameters among the groups with P<0.05 considered statistically significant.
Results: A total of 27 subjects were included in the final analysis. Subjects were treated with Bv-nivolumab-AD (n=16), Bv-AVD (n=5) and nivolumab-AVD (n=6). The distribution of MTV, TLG, and SUVmax values at PET0 and PET2 were not significantly different across the three groups. The median (IQR) ΔMTV of all study subjects was 100% (99.2%-100%), ΔTLG 100% (99.69%-100%) and ΔSUVmax 100% (68.1%-100%). Initial observation suggested that subjects receiving nivolumab-AVD had less tumor burden reduction rate compared to Bv-nivolumab-AD and Bv-AVD groups. However, this difference was not statistically significant (P=0.10) (Table 1)
Conclusion: This is the first report to describe PET-derived metabolic changes in advanced stage cHL patients receiving nivolumab and/or Bv-based regimens. Our initial results suggest a significant and comparable reduction in MTV, TLG, and SUVmax among the three treatment groups. The limited sample size did not confirm an initial observation of higher reductions in patients receiving Bv-based strategies. Future studies are needed to further explore and validate these findings.